Peptidyl aldehydes such as leupeptin, chymostatin and elastatinal are known as low-molecular enzyme inhibitors derived from natural substances. Various peptidyl aldehydes as the inhibitors are synthesized in the light of them. It is known that when the peptidyl aldehydes inhibit serine protease or thiol protease, they form a covalent bond with the hydroxyl group or thiol group of the enzyme [cf. Thompson, R. C., Biochemistry, 12, 47-51 (173)].
Since peptidyl aldehydes have an aldehyde group at the C-terminus of the peptide chain, a change in the amino acid sequence conducted in order to improve the specificity with an enzyme is limited to the N-terminus thereof. Poststatin previously found by the inventors has an .alpha.-keto amide structure in the peptide chain. The inventors continued intensive investigations thereafter on compounds having an enzymatic specificity from these points of view.
These protease-inhibiting active substances are useful as the active ingredient expected to be clinically applicable for treating autoimmune diseases, for improving the circulation in the brain, and for treating amnesia.